The mission of our Perimenopause in Brain Aging and Alzheimer's Disease Program Project (P3) is to discover the biological changes that occur in the brain during the perimenopausal transition which can result in phenotypes predictive of risk for development of Alzheimer's pathology. We seek to identify the mechanisms by which these changes occur, and translate these discoveries to determine the optimal timing and strategies for preventing conversion to the perimenopausal at-risk phenotype. To achieve our mission, we will determine the perimenopausal phenotypes associated with different cycle transition states;delineate the mechanistic pathways involved in cJevelopment of these phenotypes;and assess the impact of ovarian hormone and high-fat diet induced obesity (DIO) on expression of Alzheimer's disease biomarkers. The mission of Animal Core (Core B) is to ensure the success ofthe Perimenopause Program Project through provision of animals as neecled to Projects 1-3. To achieve its mission. Animal Core will develop rodent models of perimenopause and menopause;maintain and track animals from acquisition or birth, though determination of cycling status, study enrollment, experimental manipulation, to fissue collection across the entire Perimenopause Program Project;and obtain tissue samples for storage and genetic analyses by Analytic Core. RELEVANCE (See Instructions): The complexity of the perimenopausal process has been a major barrier to both basic and clinical research of this aging transition in women. Development of rodent models ofthe human perimenopause is critical to advancing knowledge ofthe effects ofthe perimenopause on the brain, identifying phenotypes at risk for age-associated neurological diseases, and developing strategies that promote healthy neurological aging in women to prevent age-associated diseases such as Alzheimer's.